This project seeks to elucidate the mechanisms that regulate the replication and differentiation of normal and cancer cells. The goal is the application of such knowledge to the prevention or treatment of malignant disease in humans. Significant research progress has been made in these specific areas: 1. Studies of the interaction of the transcription machinery with DNA templates using purified RNA polymerases from E. coli and wheat germ and specific cloned fragments of the DNA. 2. Molecular events in the processing of primary RNA transcripts in nuclei of eukaryotic cells. 3. Studies of the role of specific DNA sequences in the control of the promotion, termination, and anti-termination of transcription. 4. The development of genetic systems for studying embryonic development. 5. The molecular processes involved in the replication and assembly of new chromatin. 6. The mechanism of action of estrogen and glucocorticoid receptors in the regulation of gene expression. 7. The role of nuclear and cytoplasmic membranes and the phosphorylation of the constituent membrane proteins in regulation of genetic expression. 8. Studies of the interaction of tumor-promoting phorbol esters and anti-tumorigenic retinoids in the control of cell replication and differentiation. (V)